Vinyl Diazonium Ions as Synthetic Intermediates

在化学系化学合成计划的支持下，佛蒙特州大学的马蒂亚斯·布鲁尔教授正在开发新的方法来制造有机分子，使用被称为乙烯基重氮离子的化合物来实现新的碳-碳键连接。乙烯基重氮离子是一种不常见的化学构件，有可能成为重要的合成工具。布鲁尔教授和他的学生正在复杂的合成例子中测试这些化合物，并系统地确定它们的基本反应性。研究制备有机分子的创新策略是一个重要的目标，因为它使药物发现和材料科学等许多其他依赖于复杂有机分子合成的研究领域取得进展。该计划正被用于与美国化学学会(ACS)项目种子计划合作，让经济困难的高中生参与科学、技术、工程和数学(STEM)活动。布鲁尔教授还为佛蒙特州大学STEM学科的有色人种学生组织了一次年度务虚会。这一静修活动将帮助克服STEM领域有色人种学生的孤立感，让这些学生有机会在佛蒙特州大学结识并建立更大的社区感。乙烯基重氮离子是不发达的合成中间体，有可能为当前的合成挑战提供解决方案。布鲁尔教授和他的研究团队正在研究乙烯基重氮离子的反应性，以提供合成全碳四元中心的新方法，获得包含重氮官能团的复杂结构，并提供首次全合成Anadensin的策略，Anadensin是一种具有抗癌和抗微生物活性的甘蔗二萜化合物。复杂有机化合物中的全碳四元中心由于其空间位阻的性质而难以安装，但在许多生物活性分子中都有发现，包括已被证明是极好的药物先导的天然产物。人们正在研究乙烯基重氮离子作为亲电体，以提供通向全碳四元中心的新的立体选择性路线，而传统方法很难制备这些中心。重氮基是合成化学中用途最广泛的官能团之一，通过将亲核试剂与乙烯基重氮离子加成而形成的产物正被探索为后续复杂构建反应的活性合成中间体。对双环戊烯并[a，d]环辛烯5-8-5环系合成的研究正在被用于测试一种合成双环戊烯[a，d]环辛烯5-8-5环体系的新方法。这些活动协同为佛蒙特州大学不同的研究生和本科生提供了重要的合成化学培训。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Matthias Brewer of the University of Vermont is developing new ways to make organic molecules using compounds called vinyl diazonium ions to achieve new carbon-carbon bond connections. Vinyl diazonium ions are uncommon chemical building blocks with the potential to become important synthetic tools. Professor Brewer and his students are testing these compounds in complex synthetic examples and systematically establishing their fundamental reactivity. Investigating innovative strategies to prepare organic molecules is an important goal as it enables advances in many other fields of research that depend on complex organic molecule synthesis such as drug discovery and materials science. This program is being used to engage economically-disadvantaged high school students in science, technology, engineering, and mathematics (STEM) activities in collaboration with the American Chemical Society (ACS) Project SEED program. Professor Brewer is also organizing an annual retreat for University of Vermont students of color in STEM disciplines. This retreat will help to overcome the sense of isolation that students of color in STEM fields feel by providing these students a chance to meet and build a greater sense of community at the University of Vermont.Vinyl diazonium ions are underdeveloped synthetic intermediates with the potential to provide solutions to current synthetic challenges. Professor Brewer and his research team are investigating the reactivity of vinyl diazonium ions to provide new approaches to the synthesis of all-carbon quaternary centers, access complex structures that contain a diazo functional group, and provide a strategy towards the first total synthesis of anadensin, a fusicoccane diterpenoid with anti-cancer and anti-microbial activity. All-carbon quaternary centers in complex organic compounds are challenging to install due to their sterically encumbered nature but are found in many biologically active molecules including natural products that have been shown to be excellent medicinal leads. Vinyl diazonium ions are being studied as electrophiles to provide new stereoselective routes to all-carbon quaternary centers that are difficult to make by traditional methods. The diazo group is one of the most versatile functional groups in synthetic chemistry and the products formed by the addition of nucleophiles to vinyl diazonium ions are being explored as activated synthetic intermediates for subsequent complexity building reactions. Investigations towards the synthesis of anadensin are being used to test a new strategy for preparing complex dicyclopenta[a,d]cyclooctene 5-8-5 ring systems. These activities are synergistically providing important training in synthetic chemistry for a diverse group of graduate and undergraduate students at the University of Vermont.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.